hello everybody my name is Iman welcome back to my YouTube channel today we're continuing MCAT biochem prep and today's chapter is titled carbohydrate metabolism one so this is going to be the first part of carbohydrate metabolism in the next chapter will be part two now in this first part the topics that we're going to discuss in this chapter are going to be glycolysis galactose and fructose metabolism we're going to talk about pyruvate dehydrogenase we're going to talk about glycogenesis and glycog genolysis and also gluconeogenesis and finally of course the pentose phosphate pathway so those are kind of our our main topics for this chapter and kind of just start I think it's important that we know um that maintaining a constant blood glucose concentration is obviously important for us and that typical blood glucose concentration is going to be a hundred let's write this down 100 migs per D liter and so this is about a concentration of 5.6 millimolar and this kind of concentration maintaining a constant blood glucose concentration around 5.6 millimolar is obviously of the utmost importance in our bodies right because high blood glucose sugar high blood sugar causes long-term damage to many parts of our body to our retina to our kidney to our blood vessels and our nerves because there's this complex interplay between all the systems in our body that relate to the blood glucose concentrations there's a complex interplay between the endocrine system digestive system neurological system um to maintain this blood glucose concentration so it makes sense that in this chapter we're going to look at the metabolic pathways that are going to involve glucose the methods by which our bodies are going to digest glucose and other monosaccharides how do they store and release glucose for energy generate glucose how do we generate glucose from other biomolecules and how do we use glucose to create some of the coenzymes and substrates that are needed for biosynthesis so that's kind of that's kind of the introduction and description of why these topics that we're going to talk about are important now before we get to that though I do want to make a quick note right that it's that that's going to be important for you to know for the MCAT and it's also going to serve as a foundation for the rest of the chapter all right and these are the following few points before we even start with glycolysis all right first point glucose entry into most cells is going to be driven by concentration and it's independent of sodium all right two there are four glucose Transporters they're called glute one two three and four two and four are particularly interesting and the most significant why because they are located in specific cells all right and they're highly regulated now glut 2 is found in the liver all right for glucose Storage storage and the pancreatic cells and gluten four is found in edible adipose tissue and muscle and it's really stimulated by insulin all right so those are just a couple of important things mostly about glucose transport that we need to keep in mind for the MCAT and for this chapter now like I said glycolysis is going to be an important discussion here and um glycolysis along with the citric acid cycle and oxidative phosphorylation is generally identified as the process of cellular respiration now in this chapter right here carbohydrate metabolism one we're going to be focusing on glycolysis all right and in in in carbohydrate metabolism 2 chapter we're going to continue talking about cellular respiration but in that chapter we'll be focused on the citric acid cycle and obviously oxidative phosphorylation so really these two first points here right this is kind of like a summary of cellular respiration these first two points are going to be the main points of this chapter right that catabolic Pathways yield energy by oxidizing organic fuels right it's kind of what cellular respiration does and specifically that first step glycolysis it Harvest harvests chemical energy by oxidizing glucose to pyruvate now we're going to focus on these two points right the harvesting of energy from glucose bicellular respiration we've said is a cumulative function of these three stages and we're really focused on this one now typically when you learn about this you call this whole process cellular respiration sometimes people are very anal about that and really cellular respiration they will say only um deals with the citric is is only involving the citric acid cycle and oxidative phosphorylation um but today we are focusing on glycolysis but I still want to give you the whole storyline right I want to give you just a little bit of an introduction to cellular respiration in general so as we learn about each one of these three important steps it makes sense it makes sense what we're ultimately leading up to right so this is how we're going to set it up glycolysis and pyruvate oxidation is followed by the citric acid cycle and they are the catabolic Pathways that are going to break down glucose and other organic fuels glycolysis is going to occur in the cytosol all right and it begins the degradation process by breaking glucose into two molecules of a compound that we call pyruvate now in eukaryotes pyruvate is going to then enter the mitochondrion and it's gonna be oxidized to a compound that we call acetyl COA all right and that's going to be what enters the citric acid cycle and there we see the breakdown of glucose to carbon dioxide is actually completed in the citric acid cycle all right and what you produce is carbon dioxide is produced by respiration and it represents fragments of oxidized organic molecules now some of the steps of glycolysis and the citric acid cycle are redox reactions in which dehydrogenases transfer electrons from a substrate to NAD plus forming nadh and then finally in that third stage of respiration the electron transport chain accepts electrons often most often through nadh from the breakdown products of those first two stages and then it passes these electrons from one molecule to another now at the end of the chain the electrons are combined with molecular oxygen and hydrogen ions that forms water and the energy released at each step of the chain is going to be stored in the form of uh in the in a form the mitochondria can um use to make ATP from ADP and this mode of ATP synthesis is what's called oxidative phosphorylation because it is powered by redox reactions of the electron transport chain all right so that's the big picture all right and it makes sense if this doesn't make sense yet right but that's kind of what we're what we're building to right we're building to be able to understand just that all right and to do that we're going to have to be we're gonna have to cover each one of these steps in cellular respiration and now we can actually talk about how glycolysis Harvest chemical energy by oxidizing glucose to pyruvate all right now the word um glycolysis means actually Sugar splitting and you know that's exactly what happens during this pathway you know glucose is a six carbon sugar and it's going to be split into two three carbon sugars these smaller sugars are then going to be oxidized and their remaining atoms are going to be arranged to form two molecules of pyruvate so you're starting with glucose you're ending with two molecules of pyruvate now glycolysis it can technically be broken down into two steps first step is that energy investment phase and that second step is that energy payoff phase all right so the energy investment and the energy payoff phase now during the energy investment phase right that first phase what's happening well the cell is going to actually spend ATP all right and this investment is repaid with interest during the energy payoff phase why because doing the energy payoff phase ATP is produced by substrate level phosphorylation and here NAD plus is reduced to nadp nadh by electrons that are released from the oxidation of glucose and actually these two atps that you spend first all right in the energy investment phase are paid off with interest because in the energy payoff phase four atps are formed into nadh molecules are also formed all right and so the energy yield from glycolysis per single glucose molecule is the net gain then right you spent two you made four ATP the net ATP is 2 ATP and then the net nadh is 2 nadh all right so that is the energy the net energy yield from glycolysis now all of the carbon originally present in glucose is going to be accounted for in those two molecules of pyruvate that we're going to form all right so keep that in mind right all the carbon originally present in glucose is accounted for in pyruvate no carbon is released as carbon dioxide during glycolysis all right that is that can be a really good question that you can be asked in the MCAT right what is that what what are what else besides high energy yield molecules are you forming during glycolysis all right and they you know they might want to trick you by saying there's carbon dioxide there is no carbon dioxide all right there's no carbon that's released that's carbon dioxide during glycolysis now glycolysis can occur whether or not oxygen is present too however if oxygen is present the chemical energy stored in pyruvate and nadh can be extracted by pyruvate oxidation the citric acid cycle and oxidative phosphorylation now keeping all that in mind now we can actually really talk about the intricacies of of glycolysis right this is this is kind of a very broad picture image of glycolysis right we're really just looking at this so that we can extract fast information about what the net energy yield of glycolysis is but let's actually go through um the whole process in details all right so we're starting off with a glucose molecule all right then we have our first enzyme enzyme one hexokinase that transfers a phosphate group from ATP to transfers a phosphate group from ATP to glucose and it makes it more chemically reactive all right the charge on the phosphate also traps the sugar in the cell all right so that first step hexanos hexokinase I'm so sorry hexokinase takes one of the phosphate groups from ATP all right and sticks it on glucose all right so now we no longer have this ATP we have ADP instead because we stole this phosphate and we gave it to glucose now it's no longer glucose it's glucose 6-phosphate right that makes sense now then glucose 6-phosphate will then be converted to fructose 6-phosphate all right it's going to be converted to fructose 6-phosphate what helps us do that conversion this enzyme right here phospho hexos isomerase all right so that's the enzyme that helps us go from glucose 6-phosphate to fructose 6-phosphate fantastic what about the third step here now we have fructose 6-phosphate Where Do We Go From Here well then we what we have is this enzyme called phospho fructokinase and it transfers a phosphate group from ATP to the opposite end of the sugar all right we're investing a second molecule of ATP in this step this is a key step for regulation of glycolysis all right this step right here is a key is a key step for regulation of glycolysis we're using another ATP molecule so we can stick another phosphate onto our our sugar and now we have fructose one six by phosphate all right then what we have is this enzyme called aldolase all right um that is going to cleave the sugar molecule into two different sugars so it's pretty much like cutting right it's cutting that Sugar molecule that fructose one six by phosphate into two different three carbon sugars all right these are the three these are the two different three carbon sugars we have glyceraldehyde 3-phosphate and dihydroxyacetone phosphate all right now there's going to be a conversion that happens between dhap and g3p right this is g3p this is dhap all right there's going to be a conversion all right this reaction never reaches equilibrium but g3p is what's used in The Next Step because as fast as it forms like as soon as it forms it's used in The Next Step so g3p is what's moving into the next step here all right here two things are happening sugar is going to be oxidized by the transfer of electrons to NAD plus forming nadh all right the next thing that's happening after we're moving right we're moving from this step right here where we formed two different three carbon molecules all right we're moving forward with glyceraldehyde 3-phosphate all right what's happening in this next step with glyceraldehyde 3-phosphate I'm going to call it g3p from now on all right this next step what's happening all right is the sugar is going to be oxidized by the transfer of electrons and what we what happens here is we're forming nadh all right we're forming nadh and using energy from this exergonic redox reaction a phosphate group is going to be all right a phosphate group is going to be attached to the oxidized substrate making a high energy product all right so from g3p all right oxidation and phosphorylation all right now we have one three biphosphoglycerol glycerate all right now here are right here what's happening is the phosphate group is going to be transferred to a DP all right here we have a phosphate group it's going to be transferred to ADP so that we can form ATP all right this is going to happen two ad two phosphates all right to two different ADP molecules so that what we're what we're forming going from this molecule to this molecule is we're forming two ATP molecules here we form two nadhs all right so going from one three biphosphoglycerate all right two three phosphoglycerate two phosphates have been removed and added to two ADP molecules for us to make ATP all right awesome all right so fantastic all right and then we're moving we're moving this is the first ATP forming reaction substrate level all right from three phosphoglycerate to two phosphoglycerate we have phosphoglycerate mutase acting on this all right and then going from there all right this this pretty much this enzymes relocated it relocates the remaining phosphate group and then enolase comes in here all right inner lace comes in here it causes a double bond to form in the substrate pretty much by extracting a water molecule and it yields a phosphoenol pyruvate compound that's this guy right here this is also known as Pep p-e-p A compound with a very high potential energy and last but not least all right the phosphate group is going to be transferred from Pep to ADP so that we can form two more ATP molecules all right and what happens to pep is it forms pyruvate from that removal of phosphate all right so through about 10 steps we went from glucose to pyruvate all right we've used up two ATP molecules two ATP molecules were used all right but how many ATP molecules were formed four ATP molecules were formed and two nadh molecules were formed all right now you don't need to know every enzyme for glycolysis all right but you will need to know a few all right you you are going to need to know a few and so we're going to reiterate this process together here summarizing the the enzymes you definitely do need to know for the MCAT all right you need to know that glycolysis it occurs in the cytoplasm of all cells and it does not necessarily require oxygen all right it yields two ATP per molecule of glucose all right and here are the important Glide uh the the important glycolysis enzymes that you need to know all right you need to know um hexokinase all right this hexokinase enzyme that first enzyme we talked about right it converts glucose to glucose 6-phosphate all right you also need to know phosphofructure of fructo kinase as well which produces all right which produces fructose 1 6 by phosphate all right fantastic you also need to know glyceraldehyde 3-phosphate dehydrogenase this takes our g3p molecule and it converts it to 1 3 by phosphoglycerin all right and you need to know that the g3p dehydrogenase produces um nadh so this process going from g3p to 1 3 by phosphoglycerate this step particularly it's the step that produces the nadh all right fantastic you also need to know that three phosphoglycerate kinase right this one right here and and pyruvate kinase each perform what is called substrate level phosphorylation that means it places an inorganic phosphate onto ADP so that we form ATP so you really have to know what you really have to know for sure all right are the steps that use up ATP and the steps that produce nadh and the steps that produce ATP and what enzymes are doing these steps to go from one molecule to another that allows for the production of ATP that allows for the production of nadh and that and the steps also the ones that use ATP that require ATP to to move forward so you have to make sure that you know these enzymes hexokinase I'm highlighting it in red phosphofructo kinase glyceraldehyde 3-phosphate dehydrogenase um phosphoglycerate kinase um you need to know that one and then of course the last one pyruvate kinase all right make sure you know these enzymes for sure know what molecules what their their um what they're doing to each molecule that they're operating on or what they're converting them to and if they require ATP or if they produce ATP or if they produce nadh you should know that all right and it'll be easy to kind of begin to remember this as we do some of the practice problems down in the next video all right it's just going to take practice but it's going to be okay I promise all right so that is glycolysis for us now while glucose represents the primary monosaccharide that is used by cells other monosaccharides like galactose and fructose can also contribute to ATP production pretty much by feeding into glycolysis or other metabolic pathways we don't really need to know too much about this but here's the takeaway all right you can have galactose metabolism galactose comes from lactose in milk it's pretty much trapped in the Cell by galactokinase and it's converted to glucose one phosphate by this enzyme right here galactose one phosphate uradyl transferase all right and also another enzyme called eppermarase all right so that's what the main takeaway here for the galactose metabolism for the fructose well fructose comes from either honey fruit or even sucrose which is common table sugar it's trapped by the it's trapped in the Cell by fructokinase and then it's cleaved by aldolase B to form glyceraldehyde and dhp all right so it's cleaved by this to form glyceraldehyde and dhap s all right so those are kind of the main takeaways for these two other monosaccharide metal metabolic pathways that you should probably know for the MCAT now what we kind of want to talk about as a primary introduction to this topic and it'll be discussed in the next chapter as well and that's pyruvate dehydrogenation dehydrogenase um so we're going to talk about this again in the next chapter but we're going to introduce it here now pyruvate the pyruvate that's formed from aerobic glycolysis is going to enter the mitochondria where it's gonna be or it may be converted to acetyl COA all right and it's acetyl COA all right it's acetyl-coa that starts the citric acid cycle all right so that pyruvate that enters the mitochondria it can be converted to acetyl COA for entry into the citric acid cycle if ATP is needed or it can also um be used for fatty acid synthesis if there is already sufficient ATP that's present the thing that we should know here is pyruvate dehydrogenase refers to a complex of enzymes that converts pyruvate to acetyl COA and it's stimulated by insulin and inhibited by acetyl COA all right so that's important to know what is it stimulated by insulin what is it inhibited by acetyl COA all right so that's kind of what we want to say about pyruvate dehydrogenase right now we're going to go into more detail about pyruvate dehydrogenase in the next chapter now what we do really want to go into details about here in this chapter is glycogenesis and glycogenolysis please forgive my pronunciation that is a very hard word for me to say but essentially here what we're starting off with is let's define an important term for these two processes and that's glycogen glycogen is a branched polymer of glucose and it serves as a form of energy storage in animals and fungi and even bacteria and it's really similar in structure to amylopectin which is the main component of starch in plants now glycogen where it's primarily stored is in the liver and in muscle cells and it's stored there and it can be rapidly mobilized to provide energy during times of high demand the breakdown of glycogen is catalyzed by the enzymes glycogen phosphorylase and also de-branching enzymes all right so the breakdown of glycogen is catalyzed by the enzymes glycogen phosphorylase and D branching enzymes all right so the breakdown glycogen phosphorylase and de-branching enzymes conversely right the synthesis of glycogen all right the production of glycogen from glucose is catalyzed by enzymes called glycogen synthase and branching enzymes all right now glycogen metabolism is really tightly regulated in response to metabolic demand hormone signals particularly insulin and glucagon all right so we're going to talk about these two processes the production of glycogen and the breakdown of glycogen so first and foremost glucogenesis refers to the process of synthesizing glycogen from glucose all right the synthesis the production of glycogen from glucose it's catalyzed by the enzymes like we said glycogen synthase which creates an alpha 1 4 glycosidic linkage between glucose molecules and de-branching and branching enzymes I'm sorry branching enzymes all right now glycogen synthase all right let's go into a little more detail here it catalyzes the transfer of glucose from UDP glucose to the non-reducing end of a glycogen glycogen chain it pretty much requires the presence of any pre-existing glycogen primer it's going to act as a template for the synthesis of the new glyco glycogen chain all right so in short like we said glycogen synthase is just going to add glucose molecules one at a time to the non-reducing end of the primer and it's going to create an alpha 1 4 linkage between those glucose residues all right so it's it's creating this chain of glucose molecules that are attached to each other and this chain of glucose is right this branching polymer of glucose is what glycogen is all right fantastic now um glycogen synthesis is really regulated by several factors these factors are things like concentration of glucose and Insulin in the blood insulin is going to promote all right insulin promotes this insulin promotes glycogen synthesis by stimulating the activity of the enzyme glycogen synthase all right and by inhibiting the activity of glycogen phosphorylase which is going to break it down so insulin tells glycogen synthase hey bro make more glycogen and it tells glycogen phosphorylase like chill bro we don't need you to break it down glycogen all right now on the opposite end of glycogenesis is this glycogenolysis all right this is and let me erase a little bit here this is the breakdown this this word refers to the breakdown the process of breaking down glycogen into glucose one phosphate and glucose and the breakdown of glycogen is catalyzed by the enzymes glycogen phosphorylase and D branching enzymes all right glycogen phosphorylase is going to catalyze the cleavage of glycogen by breaking that alpha 1 4 glycosidic bond between glucose residues all right and it's releasing glucose 1-phosphate as a consequence de-branching enzymes are going to act on the alpha 1 6 glycosidic linkage in that glycogen molecule it actually has two function two functions it hydraulic it hydrolyzizes the alpha 1 6 glidocytic Bond and that means it releases a free glucose molecule and it also transfers the remaining chain to the alpha 1 4 position allowing glycogen phosphorylase to continue its process of breaking down the glycogen molecule this process is also regulated by several things all right including the concentration of glucose and glycogen in the blood all right glycogen is going to promote the breakdown of uh I'm sorry glucose let me repeat that this process is regulated by several factors what are those two factors concentration of glucose and concentration of glucagon all right it glucagon promotes this process by activating this enzyme right here all right and inhibiting glycogen synthesis all right so notice how these two processes that I'm going to highlight in red all right how they're the opposite one is the production of glycogen the other is the breakdown all right fantastic now we can move on to gluconeogenesis all right this is a process by which glucose is synthesized from non-carbohydrate resources such as amino acids lactate and even glycerol all right this process is important why because certain tissues in our body like our brain and our red red blood cells they're going to require a constant supply of glucose to function properly during times of fasting or when you're you know there's low carbohydrate intake gluconeogenesis is going to be activated so it can maintain your the blood glucose levels that are appropriate now this process of gluconeogenesis it involves a series of enzymatic reactions that are going to reverse many of the steps of glycolysis and that first step that you see is the conversion of pyruvate all right the that that conversion of pyruvate back to um to glucose all right so this this process is the reverse it's gonna that first conversion is going to be the conversion of pyruvate not straight to glucose I'm sorry pyruvate back to Ox uh oxaloacetate all right so what we're seeing here all right is that we're going to go through the backward steps of glycolysis the first step is the conversion of pyruvate to oxaloacetate which is catalyzed by the enzyme pyruvate carboxylase this reaction is going to require energy in the form of ATP all right in the form of ATP okay so pyruvate is going to be breaking down to oxaloacetate and then what we can what oxalo acetate is then converted to all right is phosphoenol pyruvate this is our pep molecule all right through a series of reactions that are going to require enzymes like phosphoenol pyruvate carboxy kinose this is actually kinase this is shortened as pep CK all right pep carboxy kinase all right and also Ena lace and so then oxaloacetate gets converted to pep all right pep is then converted to glucose through a series of reactions all right again that are the reverse of the last the last few steps of glycolysis all right gluconeogenesis is actually regulated by several factors this includes the concentration of substrates and hormones in the blood and the key regulatory enzyme is actually in glucose in gluconeogenesis is going to be fructose 1 6 by phosphatase all right which catalyzes the hydrolysis of fructose-16 biphosphate to fructose 6-phosphate all right this reaction is irreversible and is the rate limiting step of gluconeogenesis all right fructose 1 6 biphosphatase is inhibited by the hormone insulin but it's activated by the hormone all right so as you notice here right from Pep we can go back to like glyceraldehyde 3-phosphate back to fructose one six uh biphosphate bisphosphate all right and then this process all right this process which is regulated by fructose 1 6 boss biphosphatase all right is very important it's inhibited by the hormone insulin and activated by the hormone glucagon all right now glucose 6-phosphatase is going to convert glucose phosphate to free glucose by bypassing um glucokinase and it is only found in the endoplasmic reticulum of the liver so overall gluconeogenesis is a really important metabolic pathway that is going to allow the body to maintain blood glucose levels during the times where you might be fasting or you have low carbohydrate intake all right fantastic now last but not least all right here's a little summary by the way gluconeogenesis all right it can occur both in the cytoplasm and the mitochondria predominantly in the liver um most of gluconeogenesis is just the reverse of glycolysis it uses pretty much the same enzymes and the three irreversible steps of glycolysis have to be bypassed by different enzymes we have first and foremost pyruvate carboxylase that converts pyruvate to oxaloacetate all right which is converted to to pep by phosphoenolpyruvate carboxy kinase is another important enzyme you should know together these two enzymes are going to bypass pyruvate kinase all right and then fructose 1 6 biphosphatase is going to convert fructose one six phosphate two fructose 6-phosphate by bypassing phospho phospho fruit fructokinase one okay this is really important this is the rate limiting step of gluconeogenesis all right and it's activated by ATP directly and glucagon all right fantastic that's important this this last part you can see a lot of MCAT questions from from that statement all right now last but not least we're going to discuss the pentose phosphate pathway also known as PPP all right also known as hexa hexos monophosphate all right this occurs in the cytoplasm of all cells where it serves really two functions here all right it serves two functions the production of nadph and it serves as a source of ribose 5-phosphate for nucleotide synthesis all right so for the pentose um for the phosph the pentose phosphate pathway all right this is going to be all right one of the main one of the ways that cells can generate nadph and sugars for biosynthesis so let's kind of kind of go over this process really really quickly all right so what is the pentose phosphate pathway all right the first part of the pathway all right begins with glucose 6-phosphate all right glucose 6-phosphate and ends with right below's 5-phosphate all right and it's irreversible this part produces nadph and it involves the important rate limiting enzyme called glucose 6-phosphate dehydrogenase all right it's written right here also can be written as shorthand G6PD all right this enzyme is induced by insulin because because the abundance of sugar that enters the cell under insulin resistance will be shunted into both fuel utilization Pathways as well as fuel storage Pathways like the pentose phosphate pathway all right now this shunt is also inhibited by its product nadph and it's activated activated by one of its reactants nadp Plus the second part of the pathway begins with ribose 5-phosphate all right arrival is five five phosphate this guy right here and it represents a series of reversible reactions that are going to produce an equilibrated pool of sugars for biosynthesis this is going to include ribose 5-phosphate for nucleotide synthesis and now and and because of fructose six phosphate and glyceraldehyde 3-phosphate are among the sugars produced intermediates can also feed back into glycolysis right because you can see that we produce things like glyceraldehyde 3-phosphate all right these inter these intermediates can again like we said feedback into glycolysis or conversely pentosis can be made from glyco intermediates without going through the G6PD reaction all right and ultimately this pentose pathway pentose phosphate pathway its main purpose is to produce some nadph all right so some key Concepts really quickly I want I want to make right before we end this review and jump into the practice problems are the following points all right of all the enzymes the MCAT is most likely to test you on the rate limiting enzymes for each process are at the top of the list for glycolysis that's phosphofructu kinase one all right for fermentation that's lactate dehydrogenase for glycogenesis that's glycogen synthase for glycogenolysis that's glycogen glycogen sorry phosphorylase for gluconeogenesis that's fructose 1 6 by phosphatase and for the pentose phosphate pathway that's glucose 6-phosphate dehydrogenase so make sure you keep that in mind these enzymes are the really important ones that you should commit to memory other than that that's carbohydrate metabolism part one let me know if you have any questions comments concerns down below other than that good luck happy studying and have a beautiful beautiful day future doctors